Genetic deletion of the matrix metalloproteinase-9 enzyme (MMP-9), when coupled with a high-fat diet, exacerbates muscle insulin resistance in a mouse model of type 2 diabetes, Li Kang, Ph.D., David Wasserman, Ph.D., and colleagues report in the March issue of Diabetologia.
The researchers previously reported that diet-induced insulin resistance in these mice is associated with increased deposition of the extracellular matrix protein collagen IV and decreased activity of MMP-9, which degrades collagen IV.
While reduced MMP-9 by itself did not cause insulin resistance, the current findings support the hypothesis that, in the presence of a high-fat diet, loss of MMP-9 function leads to increased matrix deposition in muscle tissue and “a more profound state” of insulin resistance.
The study highlights a role for extracellular matrix remodeling in the development of insulin resistance. It also provides a cautionary note to those developing inhibitors of matrix metalloproteinases for the treatment of cancer and other diseases – these drugs may have an adverse effect on insulin action.
The research was supported by National Institutes of Health grants DK054902 and DK059637. The Vanderbilt Diabetes Research and Training Center is supported by DK020593.
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